Anesthesiology involves the delivery of anesthetic agents to a patient prior to and/or during a procedure; if the proper dose of anesthesia is delivered, the patient will be relieved from pain and sensory burden of the procedure with minimal side effects.
The depth of anesthesia has been historically measured subjectively by the anesthesiologist through observing various physiological variables including changes in systolic and diastolic blood pressure, heart rate or respiration rate of the patient or by observing a reflex of the eyelashes, a dimension of the pupil, a hue of a limb or the body temperature of the patient.
Anesthesia can be applied locally (delivered by transdermal, transmucosal, topical, or parental means) or delivered as a general anesthetic (delivered by inhalation, or parenteral or rectal means). Local anesthesia delivers loss of sensation to a specific region of the body while consciousness is maintained while general anesthesia causes a progressive depression of the central nervous system and a reversible loss of consciousness.
Local anesthetics are membrane stabilizing drugs which reversibly decrease the rate of depolarization and repolarization of excitable membranes. Local anesthetic drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, such as the voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic portion of the sodium channel. Local anesthetic drugs bind more readily to sodium channels in the activated state which is referred to as a state-dependent blockade, thus onset of neuronal blockade is faster in neurons that are rapidly firing.
Local anesthetics are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. At the chemical's pKa the protonated (ionized) and unprotonated (unionized) forms of the molecule exist in equilibrium but only the unprotonated molecule diffuses readily across cell membranes. Once inside the cell the local anesthetic will be in equilibrium, with the formation of the protonated (ionized form), which does not readily pass back out of the cell. In the protonated form, the molecule binds to the local anesthetic binding site on the inside of the ion channel near the cytoplasmic end.
All nerve fibers are sensitive to local anesthetics, but generally, those with a smaller diameter tend to be more sensitive than larger fibers. Local anesthetics block conduction in the following order: small myelinated axons (e.g. those carrying nociceptive impulses), non-myelinated axons, and finally large myelinated axons.
Local anesthesia can be delivered in many forms including topically (surface anesthesia), infiltration, plexus block, epidural (extradural) block and spinal anesthesia (subarachnoid block). Local anesthesia administered topically can be applied through the use of an anesthetic patch. Anesthetic patches are well known in the art and typically consist of an adhesive patch that is suitable for carrying any type of topical anesthetic.
The objectives of general anesthesia include blocking the patient's movements, relieving the patient's pain (analgesia), causing the patient to lose consciousness and be unaware of the operation and keep blood pressure above a given threshold (generally blood pressure should not be below 50 mm Hg for mean arterial pressure). General anesthesia generally produces an irregular descending paralysis of the central nervous system and suppression of the sensory cortex.
In general anesthesia the anesthesiologist administers one or more volatile liquids or gases such as nitrous oxide, isoflurane, desflurane, ethylene, cyclopropane, ether, chloroform, halothane, sevoflurane etc. Non-volatile drugs, such as pentothal, propofol, sodium thiopental, ketamine, etomydate, evipal and procaine, can alternatively be administered by injection or intravenous (IV) infusion. Onset of anesthesia is faster with intravenous administration than with inhalation taking about 10-20 seconds to induce total unconsciousness. However, inhalation is preferred in cases where IV access is difficult to obtain, where difficulty maintaining the airway is anticipated, or where the patient prefers inhalation. In order to prolong anesthesia for the duration of the surgery, the level of anesthesia used to induce the anesthetic effect must be maintained. In the case of general anesthesia administered through inhalation, the patient normally breathes in a carefully controlled combination of oxygen, nitrous oxide and a volatile anesthetic agent. Inhaled general anesthetics can be supplemented during the operation with IV anesthetics such as opiods or sedative-hypnotics.
Generally with respect to administering anesthesia through inhalation, a modern machine typically includes the following components: (1) pipeline connections to piped hospital oxygen, medical air, and nitrous oxide; (2) reserves in gas cylinders of oxygen, air, and nitrous oxide attached via a specific yoke with a Bodok seal. Older machines may have cylinder yokes and flow meters for carbon dioxide and cyclopropane; (3) a high-flow oxygen flush which provides pure oxygen at 30 liters/minute; (4) pressure gauges, regulators and ‘pop-off’ valves, to protect the machine components and patient from high-pressure gases (referred to as ‘barotrauma’); (5) flow meters (rotameters) for oxygen, air, and nitrous oxide, which are used by the anesthesiologist to provide accurate mixtures of medical gases to the patient. Flow meters are typically pneumatic, but increasingly electromagnetic digital flow meters are being used; (6) one or more anesthetic vaporizers to accurately add volatile anesthetics to the fresh gas flow; (7) a ventilator; (8) physiological monitors to monitor the patient's heart rate, ECG, non-invasive blood pressure and oxygen saturation; (9) breathing circuits, most commonly a circle attachment, or a Bain's breathing system, which are breathing hoses connected to an anesthesia face mask; (10) a heat and moisture exchanger (HME) with or without bacteria-viral filter (HMEF); (11) a scavenging system to remove expired anesthetic gases from the operating room; and (12) a suction apparatus.
Complications in anesthesia are commonly the result of an improper dose administration. For example, if a supra-optimal amount of anesthesia is delivered to the point of toxicity, morbidity or mortality can ensue whereas if a suboptimal amount of anesthesia is delivered, the patient might wake, sense pain, or develop anesthesia awareness. Neurological monitors measure neurological function but will not work properly under many general anesthesia cases nor be adequate for local anesthesia. In 2007, anesthesia complications reached 215,000 worldwide (resulting in 1,500+ deaths), 40,000 in the United States (resulting in 265 deaths), and 46,000 in Europe (resulting in 320 deaths).
The proper dose of anesthesia or analgesia is dependent on many variables that include dosage, temperature and pressure. (T. Heimburg and A. D. Jackson, “The Thermodynamics of General Anesthesia,” Biophysical Journal, vol. 92, p. 3159 (2007)). The effect of anesthesia is related to lipid membrane permeation to ions and molecules; in addition, this “permeation” may be due in part to protein channels. (A. Blicher, K. Wodzinska, M. Fidorra, M. Winterhalter, and T. Heimburg, “The temperature dependence of lipid membrane permeability, its quantized nature, and the influence of anesthetics,” Arxiv preprint arXiv:0807.4825 (2008)). Cell membrane permeability to ions and other molecules can be measured as a parameter of electromagnetic or dielectric parameters on a single, multiple or domain of frequencies. (A. Ivorra and B. Rubinsky, “In vivo electrical impedance measurements during and after electroporation of rat liver,” Bioelectrochemistry, Vol. 70, pp. 287-295 (2007)). Impedance spectroscopy can be used to measure electromagnetic or dielectric parameters by using a range of AC frequencies. Living tissue is composed of cells, which are surrounded by a lipid membrane. Between the cells, there is extracellular material that may contain extracellular fluids of varied conductivity. Electrical DC and low frequency currents are limited to the extra cellular space. With increasing AC frequency the impedance of the cell membrane decreases. The inventors have developed a method and device to measure the depth of sedation in a patient who was administered either local or general anesthesia by measuring cell permeability in tissues through impedance spectroscopy.